The proposed research will examine the mechanisms of long-term hormonal and synaptic modulation of electrical activity in identified neurons of the marine mollusc, Aplysia california. It will focus on the possible involvement of cyclic nucleotides in these long-lasting alterations. This preparation is particularly well-suited to such a study because of the presence of very large neurons, amenable to surgical manipulation, and a well-documented literature concerning neurophysiological and pharmacological relationships among neurons within the nervous system. The ionic mechanisms underlying physiological modulation of endogenous electrical activity in identified neurons will be examined by intracellular recording techniques, and compared with change induced in the same cells by perfusion and intracellular injection of substances known to alter levels of cyclic nucleotides. In addition, compartmentalization of physiological and cyclic nucleotide-induced responses between cell body and axon will be probed. Correlations between cyclic nucleotide mediation of synaptic events and pharmacological properties at individual synapses will be sought, in an attempt to determine whether particular transmitters or ionic "gates" are associated with cyclic nucleotide-linked responses in this simple nervous system.